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Involvement of angiotensinergic neurotransmissions of medial amygdaloid nucleus in control of cardiovascular and anxiogenic responses to stress in rats

Grant number: 17/19249-0
Support type:Regular Research Grants
Duration: February 01, 2018 - January 31, 2020
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Carlos Cesar Crestani
Grantee:Carlos Cesar Crestani
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Clinical and preclinical studies have provided evidence linking stress and the pathogenesis of various cardiovascular complications and psychiatric disorders. Despite the relevance of these findings, the neurobiological mechanisms involved in cardiovascular and behavioral changes evoked by stress are still poorly understood. The amygdaloid complex is an important limbic structure involved in the physiological and behavioral responses to stress. A subnucleus of amigdaloide complex activated during stress is the medial nucleus (MeA). Indeed, it has been shown an involvement of MeA on cardiovascular responses and anxiogenic effect of stress. However, the local neurochemical mechanisms involved in the control of these responses are still poorly understood. Angiotensin II acting on the AT1 receptor has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments during exposure to aversive stimuli. Data also showed that exposure to stress causes changes in the formation of angiotensin II in the central nervous system. In addition, recent data demonstrated that angiotensin 1-7/Mas receptor signaling, a counter-regulatory mechanism of angiotensin II in the renin-angiotensin system (RAS), play an inhibitory role in stress-evoked responses. Despite these pieces of evidence, the specific sites in the brain where the angiotensin II and angiotensin 1-7 act to control stress responses are not completely known. Angiotensinergic terminals and RAS components were identified in the MeA. However, a possible involvement of RAS in MeA in cardiovascular and anxiogenic responses induced by stress was never investigated. Thus, our proposal in this study is: 1) to investigate the involvement of angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor signaling mechanisms in the MeA on cardiovascular responses and anxiogenic effect induced during an acute session of restraint stress in male rats; 2) to evaluate the effect of prior repeated exposure to restraint stress in control of cardiovascular and anxiogenic responses to restraint stress by angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor in the MeA of male rats; 3) to investigate the involvement of angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor signaling MeA changes in changes on cardiovascular basal parameters and baroreflex activity induced by repeated exposure to restraint stress in male rats; and 4) to evaluate the effect of repeated exposure to restraint stress on the protein levels of AT1 and Mas receptors in the MeA in male rats. (AU)

Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C. Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 94, p. 114-124, JAN 1 2020. Web of Science Citations: 0.
GOMES-DE-SOUZA, LUCAS; COSTA-FERREIRA, WILLIAN; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C. Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling. JOURNAL OF PSYCHOPHARMACOLOGY, JAN 2020. Web of Science Citations: 0.
COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C. AT(2) and MAS (but not AT(1)) angiotensinergic receptors in the medial amygdaloid nucleus modulate the baroreflex activity in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 471, n. 9, p. 1173-1182, SEP 2019. Web of Science Citations: 0.
COSTA-FERREIRA, MILIAN; MORAIS-SILVA, GESSYNGER; GOMES-DE-SOUZA, LUCAS; MARIN, MARCELO T.; CRESTANI, CARLOS C. The AT1 Receptor Antagonist Losartan Does Not Affect Depressive-Like State and Memory Impairment Evoked by Chronic Stressors in Rats. FRONTIERS IN PHARMACOLOGY, v. 10, JUN 21 2019. Web of Science Citations: 0.
ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C. Differential roles of hippocampal nNOS and iNOS in the control of baroreflex function in conscious rats. Brain Research, v. 1710, p. 109-116, MAY 1 2019. Web of Science Citations: 1.
GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C. GAB(A) but not GABA(B) receptors in the lateral hypothalamus modulate the tachycardic response to emotional stress in rats. European Neuropsychopharmacology, v. 29, n. 5, p. 672-680, MAY 2019. Web of Science Citations: 0.
BENINI, RICARDO; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C. Habituation of the cardiovascular responses to restraint stress in male rats: influence of length, frequency and number of aversive sessions. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 22, n. 1, p. 151-161, JAN 2 2019. Web of Science Citations: 3.
VIEIRA, JONAS O.; DUARTE, JOSIANE O.; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C. Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats. PSYCHONEUROENDOCRINOLOGY, v. 97, p. 111-119, NOV 2018. Web of Science Citations: 2.

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